Fli+ etsrp+ Hemato-Vascular Progenitor Cells Proliferate at the Lateral Plate Mesoderm during Vasculogenesis in Zebrafish

Background: Vasculogenesis, the de novo formation of blood vessels from precursor cells is critical for a developing embryo. However, the signals and events that dictate the formation of primary axial vessels remain poorly understood. Methodology/Principal Findings: In this study, we use ets-related protein-1 (etsrp), which is essential for vascular development, to analyze the early stages of vasculogenesis in zebrafish. We found etsrp(+) cells of the head, trunk and tail follow distinct developmental sequences. Using a combination of genetic, molecular and chemical approaches, we demonstrate that fli(+) etsrp(+) hemato-vascular progenitors (FEVPs) are proliferating at the lateral plate mesoderm (LPM). The Shh-VEGF-Notch-Hey2 signaling pathway controls the proliferation process, and experimental modulation of single components of this pathway alters etsrp(+) cell numbers at the LPM. Conclusions/Significance: This study for the first time defines factors controlling proliferation, and cell numbers of premigratory FEVPs in zebrafish.